The invention relates to a conjugate comprising a folic acid antagonist and a carrier, a method for the production of such a conjugate as well as it""s use.
Folic acid is a compound present in nature which is important in cells for methyl group transfer and thus for the growth of cells. Folic acid has the following formula: 
The CH group of the glutamic acid represents an asymmetric C atom. Therefore, folic acid exists in two enantiomeric forms, namely as D- and L-enantiomers.
However, only the L-enantiomer from these enantiomeric forms is found in cells, so that only this form, but not the D-enantiomer, is responsible for the action of folic acid. The reason for this is that folic acid is taken up in cells by the foliate receptor, which however only takes up the L-enantiomer, but not the D-enantiomer, of folic acid.
Folic acid antagonists are compounds which are derivative from folic acid but counteract the latter at its target area, namely in cells. Therefore, folic acid antagonists are present as L-enantiomers but not as D-enantiomers. Examples of folic acid antagonists are aminomopterin and amethopterin which is also designated as methotrexate.
Methotrexate, i.e., the L-enantiomer of amethopterin, is frequently employed for the treatment of tumors and inflammations. However, major side-effects have been demonstrated for this because methotrexate is also taken up by healthy tissue and is toxic for it DE-A-41 22210.5 alone describes conjugates of methotrexate and albumin which are taken up better by tumors than by healthy tissue and are thus less toxic. Nevertheless, a great need exists for agents which have even weaker side-effects.
Therefore, the object of the present invention is to provide an agent for the treatment of diseased tissues, especially tumors, which has the weakest side-effects.
The invention relates to conjugates comprising a D-enantiomer of a folic acid antagonist and a carrier. Furthermore, the invention relates to the production of such conjugates as well as their use.